A limited number of different gram-positive bacteria, primarily viridans group streptococci, initiate colonization of the human tooth surface. These bacteria attach to host salivary components that coat the mineral surface and, through growth and interactions between species, form a relatively simple biofilm community. Members of this community can activate host cells, and the biofilm itself provides a habitat for other species, some of which are closely associated with the initiation or progression of dental caries and periodontal disease. Interactions that contribute to biofilm formation include the binding of lectin-like adhesins on Actinomyces naeslundii, Streptococcus sanguinis, Veillonella sp. and other species to specific surface carbohydrates, referred to as receptor polysaccharides (RPS), on the streptococci that initiate colonization. We hypothesize that these and other similar interactions between bacteria promote development of the characteristic oral microbial communities associated with the maintenance health or the initiation of disease.[unreadable] Seven structural types of RPS have been identified, each composed of a somewhat different hexa- or heptasaccharide repeating unit. Each repeating unit contains a host-like motif, either beta-GalNAc1-3Gal (Gn) or beta-Gal1-3GalNAc (G) that functions as a recognition site for adhesin binding, and a non-host-like, antigenic region. The adhesins present on certain oral species recognize both Gn and G types of RPS whereas those present on other species are specific for one receptor type or the other. The gene clusters for these polysaccharides encode six or seven putative glycosyltransferases, the number required for synthesis of the corresponding lipid-linked hexa- or heptasaccharide repeating unit, a flipase (Wzx), a polysaccharide polymerase (Wzy) and other genes that do not directly affect polysaccharide structure. Genes associated with the unique structural features of types 1Gn, 2Gn and 2G RPS were previously identified by structural characterization of genetically modified polysaccharides. This approach, referred to a ?carbohydrate engineering?, has now been extended to the identification and characterization the genes for type 3G RPS production by S. oralis 10557. The results of recent studies associate four new genes with the unique structural features of this polysaccharide and identify one of these as the principal genetic determinant of RPS serotype specificity. The findings illustrate a direct approach for defining the molecular basis of polysaccharide structure and function.[unreadable] In other studies, a significant difference in virulence among seven representative Streptococcus gordonii strains was noted in the rat model of infective endocarditis. Five strains, including S. gordonii DL1, caused severe disease while the other two, including S. gordonii SK12, caused minimal or no disease. This difference in virulence was evident from the visible presence of streptococci in the vegetations present on the aortic valves of catheterized rats that[unreadable] were challenged with individual strains and also from the much greater recovery of rifampicin-resistant S. gordonii DLl than streptomycin-resistant S. gordonii SK12 from the hearts of animals[unreadable] co-infected with both organisms. Each S. gordonii strain aggregated with human platelets and bound to polymorphonuclear leukocytes (PMNs) as shown by the stimulation of PMN superoxide anion production. These interactions were reduced or abolished by pretreatment of the platelets or PMNs with sialidase, thereby indicating bacterial recognition of host sialic acid-containing receptors. Adhesin-mediated binding of each S. gordonii strain to PMNs also triggered phagocytosis. However, subsequent PMN-dependent killing differed significantly among the seven strains. The five virulent strains included three that were not killed and two whose numbers were reduced by approximately 50%. In contrast, killing of each avirulent strain under the same conditions was significantly greater, approaching 90% of added bacteria. Parallel studies performed with rat PMNs revealed comparable differences in the resistance or susceptibility of representative virulent and avirulent strains. Thus, the ability of S. gordonii to survive in PMNs following adhesin-mediated phagocytosis may be an important virulence determinant of infective endocarditis. The underlying basis for the resistance or susceptibility of different S. gordonii strains to PMN-dependent killing remains to be determined. We anticipate that further progress in this area will provide important clues leading to the identification of novel virulence-associated bacterial components that may emerge as strategic targets for inhibiting bacterial pathogenesis.